Quantitative Bone Research Articles

The value of quantitative analysis of radionuclide bone SPECT/CT imaging in vertebral compression fracture: a retrospective study

BackgroundMost patients with osteoporosis experience vertebral compression fracture (VCF), which significantly reduces their quality of life. These patients are at a high risk of secondary VCF regardless of treatment. Thus, accurate diagnosis of VCF is important for treating and preventing new fractures. We aimed to investigate the diagnostic and predictive value of quantitative bone imaging techniques for fresh VCF.MethodsFrom November 2021 to March 2023, 34 patients with VCF were enrolled in this study, all of whom underwent routine 99mTc-MDP whole-body bone planar scan and local SPECT/CT imaging. The maximum standard uptake value (SUVmax) of 57 fresh VCF, 57 normal adjacent vertebrae, and 19 old VCF were measured. Based on the site of the fracture, fresh VCFs were regrouped into the intervertebral-type group and the margin-type group. Meanwhile, 52 patients who had no bone metastasis or VCFs in their bone scan were assigned to the control group. The SUVmax of 110 normal vertebral bodies and 10 old VCFs in the control group were measured.ResultsThe median SUVmax of fresh VCF was 19.80, which was significantly higher than the SUVmax of other groups. The receiver operator characteristic (ROC) curve showed that the cut-off value of SUVmax was 9.925 for diagnosing fresh VCF. The SUVmax in the intervertebral-type group was significantly higher than that in the margin-type group (P = 0.04). The SUVmax of normal vertebrae was higher among patients than among the control group (P<0.01), but the CT HU value showed no significant difference.ConclusionThe quantitative technique of bone SPECT/CT has a significant value in diagnosing fresh VCF. It can also determine the severity of fractures. In addition, whether the SUVs of the vertebrae adjacent to the fractured vertebra can predict re-fracture deserves further studies.

Mechanical Properties, Microstructure, Degradation Behavior, and Biocompatibility of Zn-0.5Ti-0.5Fe and Zn-0.5Ti-0.5Mg Guided Bone Regeneration Barrier Membranes Prepared Using a Powder Metallurgy Method.

Pure zinc exhibits low mechanical properties, making it unsuitable for use in guided bone regeneration (GBR) membranes. The present study focused on the preparation of Zn alloy GBR films using powder metallurgy, resulting in Zn-0.5Ti-0.5Fe and Zn-0.5Ti-0.5Mg alloy GBR films. The tensile strength of the pure Zn GBR film measured 85.9 MPa, while an elongation at break was 13.5%. In contrast, Zn-0.5Ti-0.5Fe and Zn-0.5Ti-0.5Mg alloy GBR films demonstrated significantly higher tensile strengths of 145.3 and 164.4 MPa, respectively, whereas elongations at break were 30.2% and 19.3%. The addition of Ti, Fe, and Mg substantially enhanced the mechanical properties of the zinc alloys. Corrosion analysis revealed that Zn-0.5Ti-0.5Fe and Zn-0.5Ti-0.5Mg alloy GBR membranes exhibited corrosion potentials of -1.298 and -1.316 V, respectively, with corresponding corrosion current densities of 12.11 and 13.32 μA/cm2. These values were translated to corrosion rates of 0.181 and 0.199 mm/year, indicating faster corrosion rates compared to pure Zn GBR membranes, which displayed a corrosion rate of 0.108 mm/year. Notably, both Zn-based alloy GBR membranes demonstrated excellent cytocompatibility, with a cytotoxicity rating of 0-1 in 25% leachate. Additionally, these membranes exhibited favorable osteogenic ability, as evidenced by the quantitative bone volume/tissue volume ratios (BV/TV) of new bone formation, which reached 30.3 ± 1.4% and 65.5 ± 1.8% for the Zn-0.5Ti-0.5Fe and Zn-0.5Ti-0.5Mg alloy GBR membranes, respectively, after 12 weeks of implantation. These results highlighted the significant potential for facilitating new bone growth. The proposed Zn-0.5Ti-0.5Fe and Zn-0.5Ti-0.5Mg alloy GBR membranes showed promise as viable biodegradable materials for future clinical studies.

Prevalence and Trends of Quantitative Bone Anomalies in Kidney Transplant Patients: A Single-Center Experience

Prevalence and Trends of Quantitative Bone Anomalies in Kidney Transplant Patients: A Single-Center Experience

Photoacoustic differential attenuation spectrum for bone assessment

Abstract Photoacoustic (PA) technology shows great potential in bone microstructure assessment. Due to the solid-liquid two-phase characteristics of cancellous bone, the PA signal received by transducers is aliasing of distributed PA source characteristics and acoustic propagation characteristics of cancellous bone. The contribution of various multi-scale distributed PA sources to the PA signal complexity leads to difficulty in identifying the sound propagation characteristics, making it difficult for quantitative assessment of bone microstructure. To eliminate the spectrum contribution of the PA source to the PA signal, we proposed an eccentric excitation-differential detection system and the acoustic propagation characteristics of cancellous bone can be obtained by calculating the PA differential attenuation spectrum (PA-DAS). The PA-DAS quantization parameter-slope is further extracted to quantify the attenuation of different frequency components. Simulation results show that slope strongly correlates to the porosity of cancellous bone, demonstrating the eccentric excitation-differential detection system combined with the PA-DAS method can realize the quantitative bone assessment.

Imaging bone turnover assessment through volumetric density-adjusted standardized uptake value using quantitative bone SPECT/CT in osteoporosis

BackgroundSerum bone turnover markers offer limited insight into metabolic activity at the individual vertebra level in osteoporosis. This study introduces a novel image-derived bone turnover marker for individual vertebrae to address this limitation, utilizing volumetric density-adjusted quantitative bone single-photon emission computed tomography/computed tomography (SPECT/CT) with [99mTc]Tc-DPD. This retrospective study included 177 lumbar vertebrae from 55 postmenopausal South Korean women. The mean standardized uptake value (SUVmean, g/cm3) and volumetric bone mineral density (vBMD, mg/cm3) were determined within a 2-cm³ volume of interest in the trabecular portion of each vertebra using quantitative SPECT and CT. The density-adjusted mean standardized uptake value (dSUVmean) was calculated by dividing the SUVmean by the vBMD and multiplying by 1,000.ResultsSUVmean correlated positively with vBMD (r = 0.60, p < 0.001). Conversely, dSUVmean correlated negatively with vBMD (ρ = −0.66, p < 0.001), highlighting the inverse relationship between bone mass and turnover after density adjustment of SUVmean. Patients with major osteoporotic fractures had lower vBMD (62.5 ± 29.4 vs. 92.3 ± 27.4 mg/cm³, p = 0.001) but higher dSUVmean (100.8 ± 60.7 vs. 62.6 ± 17.5, p = 0.001) compared to those without fractures, reinforcing the association between fracture prevalence, low bone mass, and high bone turnover.ConclusionVolumetric density-adjusted quantitative bone SPECT/CT offers a novel image-derived bone turnover marker for assessing bone turnover in osteoporosis. This method provides a precise assessment of fragility at the individual vertebra level, which may enhance personalized osteoporosis management.

Quantitative bone single photon emission computed tomography/computed tomography in symptomatic and asymptomatic foot and ankle osteoarthritis.

The purpose of this study was to evaluate and quantify the prevalence of increased uptake in SPECT/CT in symptomatic and asymptomatic foot and ankle joints in patients with osteoarthritis. In 63 patients with osteoarthritis (OA), the painful symptomatic foot (SF) and asymptomatic contralateral foot (AF) were imaged with bone SPECT/CT. Presence, localization, and maximum standardized uptake value (SUVmax) of the active joints were assessed for SF and AF. CT OA grade (grade 1: mild, grade 2: moderate, grade 3: severe) and presence of five morphological features of OA (joint space narrowing, subchondral sclerosis, subchondral cysts, irregular joint margins, and osteophytes) were evaluated. In total 32 (51%) patients showed additional uptake in the AF, whereas 31 (49%) patients showed it only in the SF. SF showed more active joints than AF (106 vs. 43). CT OA grades positively correlated with SUVmax (Kendall's tau b = 0.62, P < 0.001). SUVmax values (per foot) in SF were higher in patients with uptake in bilateral feet (SF+, AF+) [median (IQR): 17.9 (10.7-23.3)] as compared with patients with active sites only in the SF (SF+, AF-) [10.4 (6.4-19.1); P < 0.001]. Number of active OA joints in SF was higher in patients with bilateral uptake (P = 0.017). In conclusion, half of the patients exhibited increased uptake in the contralateral asymptomatic foot. SUVmax showed a significant correlation to CT osteoarthritis grade, in the symptomatic and asymptomatic foot. Future follow-up studies will provide further insights into the prognostic and therapeutic value of these findings.

Associations between leisure-time physical activity and the prevalence and incidence of osteoporosis disease: Cross-sectional and prospective findings from the UK biobank

BackgroundPrevious studies underscore the protective role of physical activity (PA) in bone health, yet the relationship between different PA categories and osteoporosis risk remains less explored. Understanding the relationships helps tailor health recommendations and policies to maximize the effects of preventing osteoporosis. MethodsThe cross-sectional study involves 488,403 UK Biobank participants with heel quantitative ultrasound-estimated bone mineral density (eBMD) data. The longitudinal cohort involves 471,394 UK Biobank participants without initial osteoporosis and with follow-up records. PA exposure categories in our study included sedentary behavior (SB), total PA (TPA), and different category-specific PA including household, leisure, and work PA. The cases of osteoporosis were assessed using the International Classification of Diseases, 10th revision (ICD-10). The linear, logistic, and Cox proportional hazard regression models were used in our study. ResultsIn the cross-sectional study, 15,818 (3.28 %) participants had osteoporosis. TPA levels have a positive correlation with eBMD and a negative correlation with osteoporosis prevalence. Among different categories of PA, higher levels of leisure PA were correlated with increased eBMD and a lower osteoporosis risk (leisure PA: OR: 0.83, 95 % CI: 0.79 to 0.86;). In the longitudinal study, 16,058 (17.6 % male, 82.4 % female) (3.41 %) individuals developed osteoporosis during an average follow-up of 13 years. We observed consistent protective effects of high levels of PA on osteoporosis incidence risk, particularly within the category of leisure PA (TPA: HR: 0.78, 95 % CI: 0.74 to 0.82; leisure PA:HR: 0.83, 95 % CI: 0.80 to 0.87). Such associations are independent of genetic predisposition, with no evidence of gene-PA interactions, and keep steady among individuals using drugs affecting bone-density. Moreover, among different leisure PA items, strenuous sports, other exercises, and walking for pleasure conferred a substantial protective effect against osteoporosis. Additionally, non-elderly individuals and males exhibited lower osteoporosis risk from PA. ConclusionThis study highlights activity categories differently associated with the risk of osteoporosis. Adherence to frequent leisure PA may have a protective effect against osteoporosis. Such associations are independent of genetic susceptibility to osteoporosis and keep steady among individuals using drugs affecting bone-density. This highlights that leisure PA could be suggested as a more effective intervention in the primary prevention of osteoporosis.

Pharmacist-initiated interventions to test quantitative bone mineral density and prescribe osteoporosis medications to prevent steroid-induced osteoporosis.

Fragility fractures associated with glucocorticoid-induced osteoporosis (GIO) can markedly impair quality of life. However, only 20% of patients are treated in compliance with the relevant management guidelines, and bone mineral density analysis with dual-energy X-ray absorptiometry (DXA) is only rarely performed. We report the intervention methods suggested by pharmacists and describe their efficacy. Patients who visited the outpatient clinic of the General Medicine Department of Ogaki Municipal Hospital and received steroids were enrolled. The rates of DXA implementation and compliance with GIO pharmacotherapy guidelines before and after pharmacist to physician-suggested interventions were compared. Guideline compliance was defined as prescription of osteoporosis drugs to patients with a score of ≥3. Administered prophylaxes and bone mineral density were subsequently assessed. The before and after intervention DXA rates were 1% (1/100 patients) and 96.0% (96/100 patients; P<0.01), respectively. Overall, 96.9% (93/96) of the patients met the GIO criteria for pharmacotherapy initiation (score ≥3), and the guideline compliance rates before and after the intervention were 39.8% (37/93) and 93.5% (87/93; P<0.01), respectively. Of the 56 patients who did not receive prophylaxis, 52 were recommended treatment, yielding an acceptance rate of 82.7% (43/52). Among the 37 patients receiving prophylaxis, 20 (54.1%) had a DXA-related young adult mean of ≤70%, of whom 11 (55.0%) agreed to drug therapy. The acceptance rate of pharmacotherapy recommendations for patients not receiving prophylaxis was higher than that for those receiving prophylaxis (P=0.03). Pharmacist-initiated interventions for GIO facilitates the administration of appropriate pharmacotherapy.

Retrospective Characterization of Bone Histomorphometric Findings in Clinical Patient Specimens.

Bone histomorphometry provides comprehensive information on bone metabolism and microstructure. In this retrospective study, we aimed to obtain an overview of the typical indications, referring hospitals, and histomorphometric quantification-based diagnoses of the bone tissue in our histomorphometry laboratory, the only laboratory in Finland carrying out histomorphometric examination of clinical bone biopsies. Between January 1, 2005 and December 31, 2020, 553 clinical bone biopsies were sent to our histomorphometry laboratory for histomorphometric examination. The median age of the patients was 55 years (range, 0.2-89.9 years), 51% of them were males, and 18% comprised pediatric patients. We received bone biopsy specimens from 23 hospitals or healthcare units. The majority of the samples we sent by nephrologists. The most common bone biopsy indications were suspicion of renal osteodystrophy (ROD), unknown bone turnover status in osteoporosis, and several or untypical fractures. The most common quantitative bone histomorphometry-based diagnosis was ROD. This study provides information on the clinical application of bone histomorphometry in Finland. Precise and quantitative ROD evaluation is the most common indication for bone histomorphometry, being crucial in clinical decision-making and targeted treatment of this patient group.

Quantitative Bone SPECT/CT of Central Cartilaginous Bone Tumors: Relationship between SUVmax and Radiodensity in Hounsfield Unit.

(1) Background: it is challenging to determine the accurate grades of cartilaginous bone tumors. Using bone single photon emission computed tomography (SPECT)/computed tomography (CT), maximum standardized uptake value (SUVmax) was found to be significantly associated with different grades of cartilaginous bone tumor. The inquiry focused on the effect of the tumor matrix on SUVmax. (2) Methods: a total of 65 patients from 2017 to 2022 with central cartilaginous bone tumors, including enchondromas and low-to-intermediate grade chondrosarcomas, who had undergone bone SPECT/CT were retrospectively enrolled. The SUVmax was recorded and any aggressive CT findings of cartilaginous bone tumor and Hounsfield units (HU) of the chondroid matrix as mean, minimum, maximum, and standard deviation (SD) were reviewed on CT scans. Pearson's correlation analysis was performed to determine the relationship between CT features and SUVmax. Subgroup analysis was also performed between the benign group (enchondroma) and the malignant group (grade 1 and 2 chondrosarcoma) for comparison of HU values and SUVmax. (3) Results: a significant negative correlation between SUVmax and HU measurements, including HUmax, HUmean, and HUSD, was found. The subgroup analysis showed significantly higher SUVmax in the malignant group, with more frequent CT aggressive features, and significantly lower HUSD in the malignant group than in the benign group. (4) Conclusions: it was observed that higher SUVmax and lower HUSD were associated with a higher probability of having a low-to-intermediate chondrosarcoma with aggressive features and a less calcified tumor matrix.

Quantitative 1H Magnetic Resonance Imaging on Normal and Pathologic Rat Bones by Solid-State 1H ZTE Sequence with Water and Fat Suppression.

Osteoporosis (OP) and osteomalacia (OM) are metabolic bone diseases characterized by mineral and matrix density changes. Quantitative bone matrix density differentiates OM from OP. MRI is a noninvasive and nonionizing imaging technique that can measure bone matrix density quantitatively in ex vivo and in vivo. To demonstrate water + fat suppressed 1H MRI to compute bone matrix density in ex vivo rat femurs in the preclinical model. Prospective. Fifteen skeletally mature female Sprague-Dawley rats, five per group (normal, ovariectomized (OVX), partially nephrectomized/vitamin D (Vit-D) deficient), 250-275 g, ∼15 weeks old. 7T, zero echo time sequence with water + fat (VAPOR) suppression capability, μCT imaging, and gravimetric measurements. Cortical and trabecular bone segments from normal and disease models were scanned in the same coil along with a dual calibration phantom for quantitative assessment of bone matrix density. ANOVA and linear regression were used for data analysis, with P-values <0.05 statistically significant. The MRI-derived three-density PEG pellet densities have a strong linear relationship with physical density measures (r2 = 0.99). The Vit-D group had the lowest bone matrix density for cortical bone (0.47 ± 0.16 g cm-3), whereas the OVX had the lowest bone matrix density for trabecular bone (0.26 ± 0.04 g cm-3). Gravimetry results confirmed these MRI-based observations for Vit-D cortical (0.51 ± 0.07 g cm-3) and OVX trabecular (0.26 ± 0.03 g cm-3) bone groups. Rat femur images were obtained using a modified pulse sequence and a custom-designed double-tuned (1H/31P) transmit-receive solenoid-coil on a 7T preclinical MRI scanner. Phantom experiments confirmed a strong linear relation between MRI-derived and physical density measures and quantitative bone matrix densities in rat femurs from normal, OVX, and Vit-D deficient/partially nephrectomized animals were computed. 2 TECHNICAL EFFICACY: Stage 2.

Periodontitis and alveolar resorption in human skeletal remains: The relationship between quantitative alveolar bone loss, occlusal wear, antemortem tooth loss, dental calculus and age at death in a low socioeconomic status, modern forensic human collection from Yucatan

ObjectiveThis paper assesses the relationship between the distance between the cemento-enamel junction and alveolar crest and risk factors commonly associated with periodontitis. MaterialsEighty individuals between 28 and 92 years old with known biological sex and age were analyzed from a 20th century forensic human collection from Merida, Yucatan (Mexico). MethodsMacroscopic assessment, along with metric analysis, was employed using a probe. ResultsAnte-mortem tooth loss was positively correlated with the distance between the cemento-enamel junction and alveolar crest, as was the presence of root calculus in females. ConclusionsCemento-enamel junction to alveolar crest distance is not a reliable indicator of periodontitis since it is not directly related to periodontitis-causing infectious pathogens, and since ante-mortem tooth loss can affect root exposure. SignificanceThis study demonstrates that a purely quantitative approach to diagnosing periodontitis in archaeological and forensic human remains can be misleading. LimitationsThe skeletal collection is only representative of the low socioeconomic class of Merida, and its female cohort is underrepresented. In addition, because the Xoclan collection is modern, limitations (particularly with respect to tooth wear) of the applicability of these interpretations to older archaeological remains exist. Suggestion for further researchA combination of quantitative and qualitative characteristics of alveolar bone is needed to reliably diagnose periodontitis in skeletal populations.

Stability of standardized uptake values for quantitative bone SPECT for jawbone lesions: a single-center cross-sectional study

BackgroundThe long time required for bone uptake of radiopharmaceutical material after injection for bone scintigraphy is a burden for patients with poor health. Thus, to assess whether the uptake time could be reduced for single-photon emission computed tomography (SPECT) of the jawbone, this study evaluated differences in maximum standardized uptake values (SUVmax) within patients using SPECT imaging at 2 and 3 hours after radiopharmaceutical injection.MethodsA total of 33 patients undergoing treatment or in post-treatment follow-up for medication-related osteonecrosis of the jaw, who visited our hospital between July 2020 and August 2021 and could receive SPECT twice on the same day, were enrolled in the study. Patients were injected with technetium-99 m hydroxymethylene diphosphonate (Tc-99 m HMDP) intravenously. The SUVmax for healthy parietal bones and jawbone lesions were calculated from the SPECT images using quantitative analysis software, and the SUVmax were compared between 2- and 3-hour uptake times.ResultsAfter exclusion, 30 patients were included in the study. In the 2-hour and 3-hour images, the median SUVmax of the parietal bones were 1.90 and 1.81, respectively, and those of the jawbone lesions were 9.25 and 9.39, respectively. The limits of agreement (LOA) ranged from − 0.33 to 0.25 in the parietal bones, and the %LOA ranged from − 9.8 to 17.3% in the jawbone lesions, showing high equivalence between the two uptake durations. The SUVmax showed no clinical differences between the 2- and 3-hour uptake durations for Tc-99 m HMDP SPECT of the jawbone.ConclusionsThe results of this study justify a 2–3-hour uptake window when performing quantitative SPECT of the jawbone. Therefore, the minimum uptake time can potentially be reduced to only 2 hours.

Prognostic value of B-score for predicting joint replacement in the context of osteoarthritis phenotypes: Data from the osteoarthritis initiative

ObjectiveDeveloping new therapies for knee osteoarthritis (KOA) requires improved prediction of disease progression. This study evaluated the prognostic value of clinical clusters and machine-learning derived quantitative 3D bone shape B-score for predicting total and partial knee replacement (KR). DesignThis retrospective study used longitudinal data from the Osteoarthritis Initiative. A previous study used patients' clinical profiles to delineate phenotypic clusters. For these clusters, the distribution of B-scores was assessed (employing Tukey's method). The value of both cluster allocation and B-score for KR-prediction was then evaluated using multivariable Cox regression models and Kaplan-Meier curves for time-to-event analyses. The impact of using B-score vs. cluster was evaluated using a likelihood ratio test for the multivariable Cox model; global performances were assessed by concordance statistics (Harrell's C-index) and time dependent receiver operating characteristic (ROC) curves. ResultsB-score differed significantly for the individual clinical clusters (p ​< ​0.001). Overall, 9.4% of participants had a KR over 9 years, with a shorter time to event in clusters with high B-score at baseline. Those clusters were characterized clinically by a high rate of comorbidities and potential signs of inflammation. Both phenotype and B-score independently predicted KR, with better prediction if combined (P ​< ​0.001). B-score added predictive value in groups with less pain and radiographic severity but limited physical activity. ConclusionsB-scores correlated with phenotypes based on clinical patient profiles. B-score and phenotype independently predicted KR surgery, with higher predictive value if combined. This can be used for patient stratification in drug development and potentially risk prediction in clinical practice.

Skeletal manifestations of anemia in the sternum in a modern clinical sample: An initial investigation

Anemia is a globally significant condition, both today and throughout history. Studying how it affected past communities contributes to understanding its impact on vulnerable groups. However, anemia diagnosis in skeletal remains is challenging, and improving methods for diagnosis is necessary for moving forward. In current clinical practice, sternal bone marrow undergoes anemia-related changes, which could affect underlying bone structure, but the sternum has never been investigated as a skeletal marker of anemia. We used a cohort of individuals with known hematological data (N = 23) to investigate whether there are quantitative bone changes in the sternum of individuals clinically diagnosed with anemia. Sternal bone features were measured using CT imaging to calculate a ratio of the relative cortical bone to trabecular space sample. The sample was separated into non-anemic and anemic cohorts based on World Health Organization diagnostic parameters. We found significant differences in ratios between those with and without anemia, suggesting that sternal bone ratio measurements could be used as a diagnostic parameter. In individuals without clinically-diagnosed anemia, ratios never exceeded 3.6 in the manubrium and 2.3 in the sternal body. We repeated these ratio measurements using micro-CT analysis on a sample of archaeological sternums and found that the ratio diagnostic parameter could also be used in this sample to identify those who could have experienced anemia. These results demonstrate the utility of quantitative methods for diagnosing anemia in skeletal remains and suggest that sternal ratio measurements can be used as part of anemia diagnosis in past contexts.

Phantomless Computed Tomography-Based Quantitative Bone Mineral Density Assessment: A Literature Review

The global surge in aging populations has intensified osteoporosis challenges, necessitating improved diagnostic methods. While dual X-ray absorptiometry (DXA) is the conventional standard in assessing bone mineral density (BMD), the exploration of quantitative computed tomography (QCT) has been proposed, particularly phantomless techniques. Challenges in single-energy CT, emphasizing internal calibration standards like subcutaneous fat, are discussed. Advances in PL-QCT, notably with automatic region of interest (ROI) selection, show improved accuracy. Dual-energy CT (DECT) introduces new dimensions for musculoskeletal analysis. Despite advancements, challenges persist, including interindividual variability and patient-specific factors. Evolving single-energy CT and DECT techniques show promise in refining BMD assessment and osteoporosis diagnosis, enhancing patient care. Continued research and integration into clinical practice are vital for realizing these advancements’ full benefits. In this review, we evaluate and summarize current evidence on the feasibility and different approaches to achieve analysis of BMD with phantomless QCT.

Pretreatment level of serum sialic acid predicts both qualitative and quantitative bone metastases of prostate cancer.

Recently, serum sialic acid (SA) has emerged as a distinct prognostic marker for prostate cancer (PCa) and bone metastases, warranting differential treatment and prognosis for low-volume (LVD) and high-volume disease (HVD). In clinical settings, evaluating bone metastases can prove advantageous. We aimed to establish the correlation between SA and both bone metastasis and HVD in newly diagnosed PCa patients. We conducted a retrospective analysis of 1202 patients who received a new diagnosis of PCa between November 2014 and February 2021. We compared pretreatment SA levels across multiple groups and investigated the associations between SA levels and the clinical parameters of patients. Additionally, we compared the differences between HVD and LVD. We utilized several statistical methods, including the non-parametric Mann-Whitney U test, Spearman correlation, receiver operating characteristic (ROC) curve analysis, and logistic regression. The results indicate that SA may serve as a predictor of bone metastasis in patients with HVD. ROC curve analysis revealed a cut-off value of 56.15 mg/dL with an area under the curve of 0.767 (95% CI: 0.703-0.832, P < 0.001) for bone metastasis versus without bone metastasis and a cut-off value of 65.80 mg/dL with an area under the curve of 0.766 (95% CI: 0.644-0.888, P = 0.003) for HVD versus LVD. Notably, PCa patients with bone metastases exhibited significantly higher SA levels than those without bone metastases, and HVD patients had higher SA levels than LVD patients. In comparison to the non-metastatic and LVD cohorts, the cohort with HVD exhibited higher levels of alkaline phosphatase (AKP) (median, 122.00 U/L), fibrinogen (FIB) (median, 3.63 g/L), and prostate-specific antigen (PSA) (median, 215.70 ng/mL), as well as higher Gleason scores (> 7). Multivariate logistic regression analysis demonstrated that an SA level of > 56.15 mg/dL was independently associated with the presence of bone metastases in PCa patients (OR = 2.966, P = 0.018), while an SA level of > 65.80 mg/dL was independently associated with HVD (OR = 1.194, P = 0.048). The pretreatment serum SA level is positively correlated with the presence of bone metastases.

Circulating and Imaging Biomarkers of Radium-223 Response in Metastatic Castration-Resistant Prostate Cancer.

Radium-223 improves overall survival (OS) and reduces skeletal events in patients with bone metastatic castration-resistant prostate cancer (CRPC), but relevant biomarkers are lacking. We evaluated automated bone scan index (aBSI) and circulating tumor cell (CTC) analyses as potential biomarkers of prognosis and activity. Patients with bone metastatic CRPC were enrolled on a prospective single-arm study of standard radium-223. 99mTc-MDP bone scan images at baseline, 2 months, and 6 months were quantitated using aBSI. CTCs at baseline, 1 month, and 2 months were enumerated and assessed for RNA expression of prostate cancer-specific genes using microfluidic enrichment followed by droplet digital polymerase chain reaction. The median OS was 21.3 months in 22 patients. Lower baseline aBSI and minimal change in aBSI (<+0.7) from baseline to 2 months were each associated with better OS (P = .00341 and P = .0139, respectively). The higher baseline CTC count of ≥5 CTC/7.5 mL was associated with worse OS (median, 10.1 v 32.9 months; P = .00568). CTCs declined at 2 months in four of 15 patients with detectable baseline CTCs. Among individual genes in CTCs, baseline expression of the splice variant AR-V7 was significantly associated with worse OS (hazard ratio, 5.20 [95% CI, 1.657 to 16.31]; P = .00195). Baseline detectable AR-V7, higher aBSI, and CTC count ≥5 CTC/7.5 mL continued to have a significant independent negative impact on OS after controlling for prostate-specific antigen or alkaline phosphatase. Quantitative bone scan assessment with aBSI and CTC analyses are prognostic markers in patients treated with radium-223. AR-V7 expression in CTCs is a particularly promising prognostic biomarker and warrants validation in larger cohorts.

The vertebrate bone hypothesis: Understanding the impact of bone on vertebrate stoichiometry

Abstract Understanding how animals store and recycle nutrients is a major question in ecological stoichiometry, a field that applies mass‐balance to ecological and physiological processes. However, ecological stoichiometry has thus far failed to accurately predict elemental demand and release in vertebrates. Because they invest in bone, a tissue mineralized with calcium phosphate, vertebrates are phosphorus (P) rich, allowing them to uniquely impact P cycling. Nonetheless, bone's impact goes further than merely changing vertebrate body elemental content. We propose a potential guiding hypothesis for vertebrate P stoichiometry called the ‘Vertebrate Bone Hypothesis (VBH)’. The VBH has three components: (1)Bone strongly impacts vertebrate whole‐body %P and N:P. (2) Bone is a P storage tissue that acts in elemental homeostasis. (3)Bone does not have constant elemental content. To characterize this hypothesis, we integrate bone physiology with stoichiometric principles, and we systematically review quantitative bone measurements to showcase cryptic diversity in vertebrate P content. Finally, we apply the characteristics of the VBH to ontogeny and reproduction, both of which impact bone physiology and elemental demand, to demonstrate the context dependency of bone's stoichiometric impact. Read the free Plain Language Summary for this article on the Journal blog.

18F-Sodium fluoride PET-CT visualizes disease activity in chronic nonbacterial osteitis in adults.

Chronic nonbacterial osteitis (CNO) is a rare disease spectrum, which lacks biomarkers for disease activity. Sodium fluoride-18 positron emission tomography/computed tomography ([18F]NaF-PET/CT) is a sensitive imaging tool for bone diseases and yields quantitative data on bone turnover. We evaluated the capacities of [18F]NaF-PET/CT to provide structural and functional assessment in adult CNO. A coss-sectional study was performed including 43 adult patients with CNO and 16 controls (patients referred for suspected, but not diagnosed with CNO) who underwent [18F]NaF-PET/CT at our expert clinic. Structural features were compared between patients and controls, and maximal standardized uptake values (SUVmax [g/mL]) were calculated for bone lesions, soft tissue/joint lesions, and reference bone. SUVmax was correlated with clinical disease activity in patients. Structural assessment revealed manubrial and costal sclerosis/hyperostosis and calcification of the costoclavicular ligament as typical features associated with CNO. SUVmax of CNO lesions was higher compared with in-patient reference bone (mean paired difference: 11.4; 95% CI: 9.4-13.5; p < .001) and controls (mean difference: 12.4; 95%CI: 9.1-15.8; p < .001). The highest SUVmax values were found in soft tissue and joint areas such as the costoclavicular ligament and manubriosternal joint, and these correlated with erythrocyte sedimentation rate in patients (correlation coefficient: 0.546; p < .002). Our data suggest that [18F]NaF-PET/CT is a promising imaging tool for adult CNO, allowing for detailed structural evaluation of its typical bone, soft-tissue, and joint features. At the same time, [18F]NaF-PET/CT yields quantitative bone remodeling data that represent the pathologically increased bone turnover and the process of new bone formation. Further studies should investigate the application of quantified [18F]NaF uptake as a novel biomarker for disease activity in CNO, and its utility to steer clinical decision making.